The overall goal of the proposed research program is to study the effects of chronic renal failure on the structure and function of the hepatic endoplasmic reticulum, particularly as regards regulation of protein synthesis, lipid metabolism and cytochrome p-450 mediated drug metabolism. In addition, the structure, function and control of ligandin in the proximal convoluted tubule will be studied, particularly as regards its role in organic anion transport. Studies will also be directed toward the mechanism whereby induction of ligandin and absence of thyroid hormone are associated with protection of the proximal convoluted tubule against injury from organic mercurials. The interdisciplinary effort involves physiologists, cell biologists and structure-function experts at an organelle level. Collaboration with Dr. Bricker's group in Miami will continue as before.